PMID- 30270457 OWN - NLM STAT- MEDLINE DCOM- 20190520 LR - 20200728 IS - 1600-0609 (Electronic) IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 102 IP - 1 DP - 2019 Jan TI - Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia. PG - 87-96 LID - 10.1111/ejh.13179 [doi] AB - OBJECTIVE: Acute myeloid leukemia (AML) can be subtyped based on recurrent cytogenetic and molecular genetic abnormalities with diagnostic and prognostic significance. Although cytogenetic characterization classically involves conventional chromosome and/or fluorescence in situ hybridization (FISH) assays, limitations of these techniques include poor resolution and the inability to precisely identify breakpoints. METHOD: We evaluated whether an NGS-based methodology that detects structural abnormalities and copy number changes using mate pair sequencing (MPseq) can enhance the diagnostic yield for patients with AML. RESULTS: Using 68 known abnormal and 20 karyotypically normal AML samples, each recurrent primary AML-specific abnormality previously identified in the abnormal samples was confirmed using MPseq. Importantly, in eight cases with abnormalities that could not be resolved by conventional cytogenetic studies, MPseq was utilized to molecularly define eight recurrent AML-fusion events. In addition, MPseq uncovered two cryptic abnormalities that were missed by conventional cytogenetic studies. Thus, MPseq improved the diagnostic yield in the detection of AML-specific structural rearrangements in 10/88 (11%) of cases analyzed. CONCLUSION: Utilization of MPseq represents a precise, molecular-based technique that can be used as an alternative to conventional cytogenetic studies for newly diagnosed AML patients with the potential to revolutionize the diagnosis of hematologic malignancies. CI - (c)2018 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd. FAU - Aypar, Umut AU - Aypar U AUID- ORCID: 0000-0002-2226-6163 AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Smoley, Stephanie A AU - Smoley SA AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Pitel, Beth A AU - Pitel BA AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Pearce, Kathryn E AU - Pearce KE AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Zenka, Roman M AU - Zenka RM AD - Bioinformatics Systems, Mayo Clinic, Rochester, Minnesota. FAU - Vasmatzis, George AU - Vasmatzis G AD - Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, Minnesota. FAU - Johnson, Sarah H AU - Johnson SH AD - Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, Minnesota. FAU - Smadbeck, James B AU - Smadbeck JB AD - Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, Minnesota. FAU - Peterson, Jess F AU - Peterson JF AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Geiersbach, Katherine B AU - Geiersbach KB AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Van Dyke, Daniel L AU - Van Dyke DL AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Thorland, Erik C AU - Thorland EC AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Jenkins, Robert B AU - Jenkins RB AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Ketterling, Rhett P AU - Ketterling RP AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Greipp, Patricia T AU - Greipp PT AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Kearney, Hutton M AU - Kearney HM AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Hoppman, Nicole L AU - Hoppman NL AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. FAU - Baughn, Linda B AU - Baughn LB AD - Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota. LA - eng GR - Mayo Clinic/ PT - Journal Article DEP - 20181122 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Oncogene Proteins, Fusion) SB - IM MH - Aged MH - *Chromosome Aberrations MH - Computational Biology/methods MH - Female MH - *Genomics/methods MH - High-Throughput Nucleotide Sequencing MH - Humans MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - Leukemia, Myeloid, Acute/*diagnosis/*genetics MH - Male MH - Oncogene Proteins, Fusion/genetics MH - *Sequence Analysis, DNA PMC - PMC7379948 OTO - NOTNLM OT - MPseq OT - acute myeloid leukemia OT - molecular cytogenetics COIS- Algorithms described in this manuscript are licensed to WholeGenome LLC owned by George Vasmatzis. EDAT- 2018/10/03 06:00 MHDA- 2019/05/21 06:00 PMCR- 2020/07/24 CRDT- 2018/10/02 06:00 PHST- 2018/07/03 00:00 [received] PHST- 2018/09/21 00:00 [revised] PHST- 2018/09/24 00:00 [accepted] PHST- 2018/10/03 06:00 [pubmed] PHST- 2019/05/21 06:00 [medline] PHST- 2018/10/02 06:00 [entrez] PHST- 2020/07/24 00:00 [pmc-release] AID - EJH13179 [pii] AID - 10.1111/ejh.13179 [doi] PST - ppublish SO - Eur J Haematol. 2019 Jan;102(1):87-96. doi: 10.1111/ejh.13179. Epub 2018 Nov 22.